T cells infiltrate the liver and kill hepatocytes in HLA-B(∗)57:01-associated floxacillin-induced liver injury.

Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.

Use of activity monitors for assessment of pruritus in an acute model of canine atopic dermatitis

BACKGROUND: We developed a canine model of acute atopic dermatitis to evaluate the potential of compounds to treat pruritus and skin lesions induced in Dermatophagoides farinae (Df)-sensitized dogs. HYPOTHESIS/OBJECTIVES: The aim was to investigate the effectiveness of long-term recording activity monitors to assess pruritus induced by allergen challenges. ANIMALS: Thirty-two Df-sensitized laboratory dogs. METHODS: In two blinded crossover studies, 28 Df-sensitized dogs were challenged on 3 days with a Df slurry applied to clipped abdominal skin. Dogs were treated with a positive control (prednisolone 1 mg/kg once daily for 5 days, starting 1 day before challenge) or left untreated; all were fitted with activity monitors. To confirm pruritus, a parallel study with four dogs was conducted, filming the dogs before and during challenge and assessing the film for pruritic behaviour. RESULTS: The activity of dogs treated with prednisolone was significantly lower between 00.00 and 03.00 h and between 03.00 and 06.00 h compared with untreated dogs (repeated-measures ANCOVA; P < 0.0001). To determine whether the recorded night-time activity corresponded to pruritic manifestations, we compared activity monitor and video recordings of four dogs for two periods (16.30-20.30 and 24.00-03.00 h) before and during a Df challenge. The correlation between night-time activity monitor activity and observed pruritic behaviour was highly significant (test of correlation coefficient versus zero: r = 0.57, P < 0.0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Determination of night-time activity with activity monitors after allergen challenge appears to be an objective and practical way to assess pruritus in this experimental model of canine atopic dermatitis.

Mus Hs 2392 - Sinfonie c-Moll, Werk 57

von Bodo Wolf

Ms. hebr. oct. 57 - ʻAḳedat Yitsḥaḳ

Vorbesitzer: Abraham Merzbacher

Ms. Barth. 57 - Expositio moralis in Historiam Scholasticam, Gen. - Lc.

Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Ms. Praed. 57 - Sermones dominicales de epistolis et evangeliis (Pars hiemalis)

Vorbesitzer: Dominikanerkloster Frankfurt am Main

Denkschrift gerichtet an Eine hohe National-Versammlung über die Gesetzes-Vorlagen No. 77, wegen Einführung und Erhöhung der Grundsteuer und über No. 57, wegen Erhöhung der Rübenzucker- und Maischsteuer

Boberach: Eine allgemeine Einkommen- und Vermögenssteuer soll anstelle der von der Regierung beabsichtigten Erhöhung der Grundsteuer aufgrund neuer Kataster und Abschaffung von Grundsteuerbefreiungen eingeführt, das gesamte Steuersystem gründlich überprüft werden. Die Fabrikation von Alkohol aus Kartoffeln darf nicht mit der Maischsteuer gefährdet werden. In der Anlage: Durchschnittliche Tagesbetriebskosten einer größeren preußischen Branntweinbrennerei

The impact of associational life on trust in local institutions: a comparison of 57 Swiss municipalities

In this paper, we evaluate the impact of associational life on individual political trust in 57 Swiss municipalities. Our hierarchical regression models show that individual political trust is not only affected by individual associational membership but also by the exchange between associations and local political authorities in a community. In other words, if political authorities and associations are linked at the community level, citizens will place more trust in their local institutions. Furthermore, we find clear evidence for the rainmaker hypothesis: our results show that the positive effect of a vibrant connection between associational life and local politics on political trust is not solely confined to the associational members themselves, but rather indicate that the structure of the local civic culture fosters political trust among members and non-members at the same time. However, the internal democratic processes of associations have no effect on individuals’ trust in local political institutions.

Der Propheten-Abschnitt von Jom-Kippur : Jesaja 57, 14 und 58

Buber-Rosenzweig

Jom-Kippur-Morgen : Erklärung der Hastoroh Jeschajohu 57 - 58

Raphael Levi

Abraham ibn Esra zu Ex 25, 10 und Jesaja 57, 9

David Herzog

[Todesanzeige für] Herrn Henrich Nicolaus Rückersfelder [verstorben ...] am 14. Octobr., a. c. [1747] im 57. Jahr seines Alters und 28. seiner öffentlichen Amts-Bedienung ...

Eingebunden in: Senckenberg, Johann Christian: Ärztliches Tagebuch: März 1743 - Februar 1744

Ms. germ. fol. 57 - Vorstellung und Bitte von Seiten des Vorstandes des israelitschen Gemeinde, die Ehen hiesiger Israeliten mit Fremden betreffend. Anlage: Verzeichnis aller seit Anfang des Jahres 1825 von hier ins Ausland verheiratheten Mannes- und Frauenspersonen unter Angabe des Jahrs ihrer Verehelichung

Alte Signatur: Jud. Ff. 50; Akzessionsnummer: 1333/17

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 441 - Fragment eines alphabetischen Registers zu den Studienbüchern

u.a.: Register mit den Buchstaben A und B;